                         SEQUENCE LISTING

<110>  Fundaci Privada Institut dInvestigaci Oncolgica de Vall
        Hebron
       FUNDACIN SOLTI
       Fundacin para el Fomento de la Investigacin Sanitaria y 
       Biomdica de la Comunitat Valenciana (FISABIO)
       Hospital Clinic de Barcelona
 
<120>  HER2 as a predictor of response to dual HER2 blockade in the 
       absence of cytotoxic therapy

<130>  P3795PC00

<160>  3     

<170>  PatentIn version 3.5

<210>  1
<211>  4816
<212>  DNA
<213>  Homo sapiens

<400>  1
gttcccggat ttttgtgggc gcctgccccg cccctcgtcc ccctgctgtg tccatatatc       60

gaggcgatag ggttaaggga aggcggacgc ctgatgggtt aatgagcaaa ctgaagtgtt      120

ttccatgatc ttttttgagt cgcaattgaa gtaccacctc ccgagggtga ttgcttcccc      180

atgcggggta gaacctttgc tgtcctgttc accactctac ctccagcaca gaatttggct      240

tatgcctact caatgtgaag atgatgagga tgaaaacctt tgtgatgatc cacttccact      300

taatgaatgg tggcaaagca aagctatatt caagaccaca tgcaaagcta ctccctgagc      360

aaagagtcac agataaaacg ggggcaccag tagaatggcc aggacaaacg cagtgcagca      420

cagagactca gaccctggca gccatgcctg cgcaggcagt gatgagagtg acatgtactg      480

ttgtggacat gcacaaaagt gagtgtgcac cggcacagac atgaagctgc ggctccctgc      540

cagtcccgag acccacctgg acatgctccg ccacctctac cagggctgcc aggtggtgca      600

gggaaacctg gaactcacct acctgcccac caatgccagc ctgtccttcc tgcaggatat      660

ccaggaggtg cagggctacg tgctcatcgc tcacaaccaa gtgaggcagg tcccactgca      720

gaggctgcgg attgtgcgag gcacccagct ctttgaggac aactatgccc tggccgtgct      780

agacaatgga gacccgctga acaataccac ccctgtcaca ggggcctccc caggaggcct      840

gcgggagctg cagcttcgaa gcctcacaga gatcttgaaa ggaggggtct tgatccagcg      900

gaacccccag ctctgctacc aggacacgat tttgtggaag gacatcttcc acaagaacaa      960

ccagctggct ctcacactga tagacaccaa ccgctctcgg gcctgccacc cctgttctcc     1020

gatgtgtaag ggctcccgct gctggggaga gagttctgag gattgtcaga gcctgacgcg     1080

cactgtctgt gccggtggct gtgcccgctg caaggggcca ctgcccactg actgctgcca     1140

tgagcagtgt gctgccggct gcacgggccc caagcactct gactgcctgg cctgcctcca     1200

cttcaaccac agtggcatct gtgagctgca ctgcccagcc ctggtcacct acaacacaga     1260

cacgtttgag tccatgccca atcccgaggg ccggtataca ttcggcgcca gctgtgtgac     1320

tgcctgtccc tacaactacc tttctacgga cgtgggatcc tgcaccctcg tctgccccct     1380

gcacaaccaa gaggtgacag cagaggatgg aacacagcgg tgtgagaagt gcagcaagcc     1440

ctgtgcccga gtgtgctatg gtctgggcat ggagcacttg cgagaggtga gggcagttac     1500

cagtgccaat atccaggagt ttgctggctg caagaagatc tttgggagcc tggcatttct     1560

gccggagagc tttgatgggg acccagcctc caacactgcc ccgctccagc cagagcagct     1620

ccaagtgttt gagactctgg aagagatcac aggttaccta tacatctcag catggccgga     1680

cagcctgcct gacctcagcg tcttccagaa cctgcaagta atccggggac gaattctgca     1740

caatggcgcc tactcgctga ccctgcaagg gctgggcatc agctggctgg ggctgcgctc     1800

actgagggaa ctgggcagtg gactggccct catccaccat aacacccacc tctgcttcgt     1860

gcacacggtg ccctgggacc agctctttcg gaacccgcac caagctctgc tccacactgc     1920

caaccggcca gaggacgagt gtgtgggcga gggcctggcc tgccaccagc tgtgcgcccg     1980

agggcactgc tggggtccag ggcccaccca gtgtgtcaac tgcagccagt tccttcgggg     2040

ccaggagtgc gtggaggaat gccgagtact gcaggggctc cccagggagt atgtgaatgc     2100

caggcactgt ttgccgtgcc accctgagtg tcagccccag aatggctcag tgacctgttt     2160

tggaccggag gctgaccagt gtgtggcctg tgcccactat aaggaccctc ccttctgcgt     2220

ggcccgctgc cccagcggtg tgaaacctga cctctcctac atgcccatct ggaagtttcc     2280

agatgaggag ggcgcatgcc agccttgccc catcaactgc acccactcct gtgtggacct     2340

ggatgacaag ggctgccccg ccgagcagag agccagccct ctgacgtcca tcatctctgc     2400

ggtggttggc attctgctgg tcgtggtctt gggggtggtc tttgggatcc tcatcaagcg     2460

acggcagcag aagatccgga agtacacgat gcggagactg ctgcaggaaa cggagctggt     2520

ggagccgctg acacctagcg gagcgatgcc caaccaggcg cagatgcgga tcctgaaaga     2580

gacggagctg aggaaggtga aggtgcttgg atctggcgct tttggcacag tctacaaggg     2640

catctggatc cctgatgggg agaatgtgaa aattccagtg gccatcaaag tgttgaggga     2700

aaacacatcc cccaaagcca acaaagaaat cttagacgaa gcatacgtga tggctggtgt     2760

gggctcccca tatgtctccc gccttctggg catctgcctg acatccacgg tgcagctggt     2820

gacacagctt atgccctatg gctgcctctt agaccatgtc cgggaaaacc gcggacgcct     2880

gggctcccag gacctgctga actggtgtat gcagattgcc aaggggatga gctacctgga     2940

ggatgtgcgg ctcgtacaca gggacttggc cgctcggaac gtgctggtca agagtcccaa     3000

ccatgtcaaa attacagact tcgggctggc tcggctgctg gacattgacg agacagagta     3060

ccatgcagat gggggcaagg tgcccatcaa gtggatggcg ctggagtcca ttctccgccg     3120

gcggttcacc caccagagtg atgtgtggag ttatggtgtg actgtgtggg agctgatgac     3180

ttttggggcc aaaccttacg atgggatccc agcccgggag atccctgacc tgctggaaaa     3240

gggggagcgg ctgccccagc cccccatctg caccattgat gtctacatga tcatggtcaa     3300

atgttggatg attgactctg aatgtcggcc aagattccgg gagttggtgt ctgaattctc     3360

ccgcatggcc agggaccccc agcgctttgt ggtcatccag aatgaggact tgggcccagc     3420

cagtcccttg gacagcacct tctaccgctc actgctggag gacgatgaca tgggggacct     3480

ggtggatgct gaggagtatc tggtacccca gcagggcttc ttctgtccag accctgcccc     3540

gggcgctggg ggcatggtcc accacaggca ccgcagctca tctaccagga gtggcggtgg     3600

ggacctgaca ctagggctgg agccctctga agaggaggcc cccaggtctc cactggcacc     3660

ctccgaaggg gctggctccg atgtatttga tggtgacctg ggaatggggg cagccaaggg     3720

gctgcaaagc ctccccacac atgaccccag ccctctacag cggtacagtg aggaccccac     3780

agtacccctg ccctctgaga ctgatggcta cgttgccccc ctgacctgca gcccccagcc     3840

tgaatatgtg aaccagccag atgttcggcc ccagccccct tcgccccgag agggccctct     3900

gcctgctgcc cgacctgctg gtgccactct ggaaaggccc aagactctct ccccagggaa     3960

gaatggggtc gtcaaagacg tttttgcctt tgggggtgcc gtggagaacc ccgagtactt     4020

gacaccccag ggaggagctg cccctcagcc ccaccctcct cctgccttca gcccagcctt     4080

cgacaacctc tattactggg accaggaccc accagagcgg ggggctccac ccagcacctt     4140

caaagggaca cctacggcag agaacccaga gtacctgggt ctggacgtgc cagtgtgaac     4200

cagaaggcca agtccgcaga agccctgatg tgtcctcagg gagcagggaa ggcctgactt     4260

ctgctggcat caagaggtgg gagggccctc cgaccacttc caggggaacc tgccatgcca     4320

ggaacctgtc ctaaggaacc ttccttcctg cttgagttcc cagatggctg gaaggggtcc     4380

agcctcgttg gaagaggaac agcactgggg agtctttgtg gattctgagg ccctgcccaa     4440

tgagactcta gggtccagtg gatgccacag cccagcttgg ccctttcctt ccagatcctg     4500

ggtactgaaa gccttaggga agctggcctg agaggggaag cggccctaag ggagtgtcta     4560

agaacaaaag cgacccattc agagactgtc cctgaaacct agtactgccc cccatgagga     4620

aggaacagca atggtgtcag tatccaggct ttgtacagag tgcttttctg tttagttttt     4680

actttttttg ttttgttttt ttaaagatga aataaagacc cagggggaga atgggtgttg     4740

tatggggagg caagtgtggg gggtccttct ccacacccac tttgtccatt tgcaaatata     4800

ttttggaaaa cagcta                                                     4816


<210>  2
<211>  1225
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Lys Leu Arg Leu Pro Ala Ser Pro Glu Thr His Leu Asp Met Leu 
1               5                   10                  15      


Arg His Leu Tyr Gln Gly Cys Gln Val Val Gln Gly Asn Leu Glu Leu 
            20                  25                  30          


Thr Tyr Leu Pro Thr Asn Ala Ser Leu Ser Phe Leu Gln Asp Ile Gln 
        35                  40                  45              


Glu Val Gln Gly Tyr Val Leu Ile Ala His Asn Gln Val Arg Gln Val 
    50                  55                  60                  


Pro Leu Gln Arg Leu Arg Ile Val Arg Gly Thr Gln Leu Phe Glu Asp 
65                  70                  75                  80  


Asn Tyr Ala Leu Ala Val Leu Asp Asn Gly Asp Pro Leu Asn Asn Thr 
                85                  90                  95      


Thr Pro Val Thr Gly Ala Ser Pro Gly Gly Leu Arg Glu Leu Gln Leu 
            100                 105                 110         


Arg Ser Leu Thr Glu Ile Leu Lys Gly Gly Val Leu Ile Gln Arg Asn 
        115                 120                 125             


Pro Gln Leu Cys Tyr Gln Asp Thr Ile Leu Trp Lys Asp Ile Phe His 
    130                 135                 140                 


Lys Asn Asn Gln Leu Ala Leu Thr Leu Ile Asp Thr Asn Arg Ser Arg 
145                 150                 155                 160 


Ala Cys His Pro Cys Ser Pro Met Cys Lys Gly Ser Arg Cys Trp Gly 
                165                 170                 175     


Glu Ser Ser Glu Asp Cys Gln Ser Leu Thr Arg Thr Val Cys Ala Gly 
            180                 185                 190         


Gly Cys Ala Arg Cys Lys Gly Pro Leu Pro Thr Asp Cys Cys His Glu 
        195                 200                 205             


Gln Cys Ala Ala Gly Cys Thr Gly Pro Lys His Ser Asp Cys Leu Ala 
    210                 215                 220                 


Cys Leu His Phe Asn His Ser Gly Ile Cys Glu Leu His Cys Pro Ala 
225                 230                 235                 240 


Leu Val Thr Tyr Asn Thr Asp Thr Phe Glu Ser Met Pro Asn Pro Glu 
                245                 250                 255     


Gly Arg Tyr Thr Phe Gly Ala Ser Cys Val Thr Ala Cys Pro Tyr Asn 
            260                 265                 270         


Tyr Leu Ser Thr Asp Val Gly Ser Cys Thr Leu Val Cys Pro Leu His 
        275                 280                 285             


Asn Gln Glu Val Thr Ala Glu Asp Gly Thr Gln Arg Cys Glu Lys Cys 
    290                 295                 300                 


Ser Lys Pro Cys Ala Arg Val Cys Tyr Gly Leu Gly Met Glu His Leu 
305                 310                 315                 320 


Arg Glu Val Arg Ala Val Thr Ser Ala Asn Ile Gln Glu Phe Ala Gly 
                325                 330                 335     


Cys Lys Lys Ile Phe Gly Ser Leu Ala Phe Leu Pro Glu Ser Phe Asp 
            340                 345                 350         


Gly Asp Pro Ala Ser Asn Thr Ala Pro Leu Gln Pro Glu Gln Leu Gln 
        355                 360                 365             


Val Phe Glu Thr Leu Glu Glu Ile Thr Gly Tyr Leu Tyr Ile Ser Ala 
    370                 375                 380                 


Trp Pro Asp Ser Leu Pro Asp Leu Ser Val Phe Gln Asn Leu Gln Val 
385                 390                 395                 400 


Ile Arg Gly Arg Ile Leu His Asn Gly Ala Tyr Ser Leu Thr Leu Gln 
                405                 410                 415     


Gly Leu Gly Ile Ser Trp Leu Gly Leu Arg Ser Leu Arg Glu Leu Gly 
            420                 425                 430         


Ser Gly Leu Ala Leu Ile His His Asn Thr His Leu Cys Phe Val His 
        435                 440                 445             


Thr Val Pro Trp Asp Gln Leu Phe Arg Asn Pro His Gln Ala Leu Leu 
    450                 455                 460                 


His Thr Ala Asn Arg Pro Glu Asp Glu Cys Val Gly Glu Gly Leu Ala 
465                 470                 475                 480 


Cys His Gln Leu Cys Ala Arg Gly His Cys Trp Gly Pro Gly Pro Thr 
                485                 490                 495     


Gln Cys Val Asn Cys Ser Gln Phe Leu Arg Gly Gln Glu Cys Val Glu 
            500                 505                 510         


Glu Cys Arg Val Leu Gln Gly Leu Pro Arg Glu Tyr Val Asn Ala Arg 
        515                 520                 525             


His Cys Leu Pro Cys His Pro Glu Cys Gln Pro Gln Asn Gly Ser Val 
    530                 535                 540                 


Thr Cys Phe Gly Pro Glu Ala Asp Gln Cys Val Ala Cys Ala His Tyr 
545                 550                 555                 560 


Lys Asp Pro Pro Phe Cys Val Ala Arg Cys Pro Ser Gly Val Lys Pro 
                565                 570                 575     


Asp Leu Ser Tyr Met Pro Ile Trp Lys Phe Pro Asp Glu Glu Gly Ala 
            580                 585                 590         


Cys Gln Pro Cys Pro Ile Asn Cys Thr His Ser Cys Val Asp Leu Asp 
        595                 600                 605             


Asp Lys Gly Cys Pro Ala Glu Gln Arg Ala Ser Pro Leu Thr Ser Ile 
    610                 615                 620                 


Ile Ser Ala Val Val Gly Ile Leu Leu Val Val Val Leu Gly Val Val 
625                 630                 635                 640 


Phe Gly Ile Leu Ile Lys Arg Arg Gln Gln Lys Ile Arg Lys Tyr Thr 
                645                 650                 655     


Met Arg Arg Leu Leu Gln Glu Thr Glu Leu Val Glu Pro Leu Thr Pro 
            660                 665                 670         


Ser Gly Ala Met Pro Asn Gln Ala Gln Met Arg Ile Leu Lys Glu Thr 
        675                 680                 685             


Glu Leu Arg Lys Val Lys Val Leu Gly Ser Gly Ala Phe Gly Thr Val 
    690                 695                 700                 


Tyr Lys Gly Ile Trp Ile Pro Asp Gly Glu Asn Val Lys Ile Pro Val 
705                 710                 715                 720 


Ala Ile Lys Val Leu Arg Glu Asn Thr Ser Pro Lys Ala Asn Lys Glu 
                725                 730                 735     


Ile Leu Asp Glu Ala Tyr Val Met Ala Gly Val Gly Ser Pro Tyr Val 
            740                 745                 750         


Ser Arg Leu Leu Gly Ile Cys Leu Thr Ser Thr Val Gln Leu Val Thr 
        755                 760                 765             


Gln Leu Met Pro Tyr Gly Cys Leu Leu Asp His Val Arg Glu Asn Arg 
    770                 775                 780                 


Gly Arg Leu Gly Ser Gln Asp Leu Leu Asn Trp Cys Met Gln Ile Ala 
785                 790                 795                 800 


Lys Gly Met Ser Tyr Leu Glu Asp Val Arg Leu Val His Arg Asp Leu 
                805                 810                 815     


Ala Ala Arg Asn Val Leu Val Lys Ser Pro Asn His Val Lys Ile Thr 
            820                 825                 830         


Asp Phe Gly Leu Ala Arg Leu Leu Asp Ile Asp Glu Thr Glu Tyr His 
        835                 840                 845             


Ala Asp Gly Gly Lys Val Pro Ile Lys Trp Met Ala Leu Glu Ser Ile 
    850                 855                 860                 


Leu Arg Arg Arg Phe Thr His Gln Ser Asp Val Trp Ser Tyr Gly Val 
865                 870                 875                 880 


Thr Val Trp Glu Leu Met Thr Phe Gly Ala Lys Pro Tyr Asp Gly Ile 
                885                 890                 895     


Pro Ala Arg Glu Ile Pro Asp Leu Leu Glu Lys Gly Glu Arg Leu Pro 
            900                 905                 910         


Gln Pro Pro Ile Cys Thr Ile Asp Val Tyr Met Ile Met Val Lys Cys 
        915                 920                 925             


Trp Met Ile Asp Ser Glu Cys Arg Pro Arg Phe Arg Glu Leu Val Ser 
    930                 935                 940                 


Glu Phe Ser Arg Met Ala Arg Asp Pro Gln Arg Phe Val Val Ile Gln 
945                 950                 955                 960 


Asn Glu Asp Leu Gly Pro Ala Ser Pro Leu Asp Ser Thr Phe Tyr Arg 
                965                 970                 975     


Ser Leu Leu Glu Asp Asp Asp Met Gly Asp Leu Val Asp Ala Glu Glu 
            980                 985                 990         


Tyr Leu Val Pro Gln Gln Gly Phe  Phe Cys Pro Asp Pro  Ala Pro Gly 
        995                 1000                 1005             


Ala Gly  Gly Met Val His His  Arg His Arg Ser Ser  Ser Thr Arg 
    1010                 1015                 1020             


Ser Gly  Gly Gly Asp Leu Thr  Leu Gly Leu Glu Pro  Ser Glu Glu 
    1025                 1030                 1035             


Glu Ala  Pro Arg Ser Pro Leu  Ala Pro Ser Glu Gly  Ala Gly Ser 
    1040                 1045                 1050             


Asp Val  Phe Asp Gly Asp Leu  Gly Met Gly Ala Ala  Lys Gly Leu 
    1055                 1060                 1065             


Gln Ser  Leu Pro Thr His Asp  Pro Ser Pro Leu Gln  Arg Tyr Ser 
    1070                 1075                 1080             


Glu Asp  Pro Thr Val Pro Leu  Pro Ser Glu Thr Asp  Gly Tyr Val 
    1085                 1090                 1095             


Ala Pro  Leu Thr Cys Ser Pro  Gln Pro Glu Tyr Val  Asn Gln Pro 
    1100                 1105                 1110             


Asp Val  Arg Pro Gln Pro Pro  Ser Pro Arg Glu Gly  Pro Leu Pro 
    1115                 1120                 1125             


Ala Ala  Arg Pro Ala Gly Ala  Thr Leu Glu Arg Pro  Lys Thr Leu 
    1130                 1135                 1140             


Ser Pro  Gly Lys Asn Gly Val  Val Lys Asp Val Phe  Ala Phe Gly 
    1145                 1150                 1155             


Gly Ala  Val Glu Asn Pro Glu  Tyr Leu Thr Pro Gln  Gly Gly Ala 
    1160                 1165                 1170             


Ala Pro  Gln Pro His Pro Pro  Pro Ala Phe Ser Pro  Ala Phe Asp 
    1175                 1180                 1185             


Asn Leu  Tyr Tyr Trp Asp Gln  Asp Pro Pro Glu Arg  Gly Ala Pro 
    1190                 1195                 1200             


Pro Ser  Thr Phe Lys Gly Thr  Pro Thr Ala Glu Asn  Pro Glu Tyr 
    1205                 1210                 1215             


Leu Gly  Leu Asp Val Pro Val  
    1220                 1225 


<210>  3
<211>  100
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target sequence of ERBB2

<400>  3
acagacacgt ttgagtccat gcccaatccc gagggccggt atacattcgg cgccagctgt       60

gtgactgcct gtccctacaa ctacctttct acggacgtgg                            100


